Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract disease in young children worldwide, and is also a major cause of morbidity in the elderly and immunocompromised populations. No approved RSV vaccine exists. Our goal is to define broadly protecting antibody epitopes on RSV G protein. RSV G protein is one of two major immunogenic proteins on the RSV surface and plays key roles in virus attachment to airway epithelial cells and virus modulation of innate immune defenses. Despite the important role of RSV G protein in infection and pathogenesis, little is known about the structural and molecular features that govern its activities. Our central hypothesis is that the central conserved region of RSV G protein contains both linear and conformational epitopes for broadly protecting antibodies. Using an integrated structural and biophysical approach, we will pursue two specific aims to (1) Identify RSV G protein constructs that maintain high-affinity binding to anti-G antibodies and (2) Use structural studies to define epitopes on RSV G protein recognized by broadly protecting antibodies. Results obtained by this work will provide a molecular roadmap for the development of novel RSV G vaccine immunogens to prevent RSV infection and disease.